Self-Assembly and Neurotoxicity of β-Amyloid (21–40) Peptide Fragment: The Regulatory Role of GxxxG Motifs

The three GxxxG repeating motifs from the C-terminal region of β-amyloid (Aβ) peptide play a significant role in regulating the aggregation kinetics of the peptide. Mutation of these glycine residues to leucine greatly accelerates the fibrillation process but generates a varied toxicity profile. Using an array of biophysical techniques, we demonstrated the uniqueness of the composite glycine residues in these structural repeats. We used solvent relaxation NMR spectroscopy to investigate the role played by the surrounding water molecules in determining the corresponding aggregation pathway. Notably, the conformational changes induced by Gly³³ and Gly³⁷ mutations result in significantly decreased toxicity in a neuronal cell line. Our results indicate that G³³xxxG³⁷ is the primary motif responsible for Aβ neurotoxicity, hence providing a direct structure–function correlation. Targeting this motif, therefore, can be a promising strategy to prevent neuronal cell death associated with Alzheimer's and other related diseases, such as type II diabetes and Parkinson's.     

Effects of extracts of spices on rumen methanogenesis,enzyme activities and fermentation of feeds in vitro

BACKGROUND: An experiment was conducted to study the effects of boiling water, methanol and ethanol extracts (0, 0.25 and 0.50 mL) of seeds of Foeniculum vulgare (fennel), flower buds of Syzygium aromaticum (clove), bulbs of Allium sativum (garlic), bulbs of Allium cepa (onion) and roots of Zingiber officinalis (ginger) on rumen methanogenesis, fibrolytic enzyme activities and fermentation characteristics in vitro. RESULTS: Ethanol and methanol extracts of fennel, clove and garlic at 0.50 mL and clove at 0.25 mL inhibited (P < 0.05) methane production. Carboxymethylcellulase activity was reduced (P < 0.05) by ethanol and methanol extracts (0.50 mL) of fennel and clove (0.25 and 0.50 mL). The extracts of clove reduced (0.25 and 0.50 mL) xylanase and acetylesterase activities, and the fennel extract (0.50 mL) reduced (P < 0.05) xylanase activity. However, the extracts of garlic (0.50 mL) increased (P < 0.05) acetylesterase activity. Concentrations of volatile fatty acids were reduced (P < 0.05) by the extracts of garlic and onion. The extracts of garlic caused a decrease (P < 0.05) in acetate:propionate ratio (A:P) at 0.50 mL, whereas A:P was increased (P < 0.05) by the inclusion of 0.50 mL extracts of clove. Methanol and ethanol extracts of clove decreased (P < 0.05) in vitro organic matter degradability. Extracts (0.50 mL) of clove decreased (P < 0.05) the numbers of total protozoa, small entodiniomorphs and holotrichs, whereas extracts of onion, ginger and garlic enhanced (P < 0.05) protozoal numbers (both entodiniomorphs and holotrichs). CONCLUSION: Ethanol and methanol extracts of fennel and garlic have potential to inhibit rumen methanogenesis without adversely affecting rumen fermentation. Copyright © 2009 Society of Chemical Industry     

Symposium review: The importance of the ruminal epithelial barrier for a healthy and productive cow

The stratified squamous ruminal epithelium is the main site for absorption of key nutrients (e.g., short-chain fatty acids; SCFA) and electrolytes (e.g., sodium and magnesium). The absorptive function has to be highly selective to prevent simultaneous entry of microbes and toxins from the rumen into the blood. As such, epithelial absorption is primarily transcellular, whereas the paracellular pathway appears rather tightly sealed. A network of tight junction (claudin-1, claudin-4, and occludin) and tight junction-associated proteins (e.g., zonula occludens) accomplishes the latter. When microbial fermentation activity is high such as with highly fermentable diets, rumen epithelial functions are often challenged by acidity, high osmolarity, toxins (e.g., endotoxin and histamine), and immune mediators (inflammatory mediators and cytokines) released during local and systemic inflammation. Epithelial damage by low pH in combination with high luminal SCFA concentrations is not immediately reversible and may initially aggravate upon return to physiological pH. In contrast, barrier opening upon hyperosmolarity is acutely transient. The initial insults set by luminal acidity and SCFA and the increasing concentrations of microbial-associated molecular patterns such as lipopolysaccharides are key factors that trigger inflammation not only in the rumen but also in the hindgut (cecum and colon), which reach out to the liver and other organs, causing systemic inflammation. Low feed intake during parturition, transportation, heat stress, or disease is the second most relevant challenge for the ruminal epithelial barrier. The barrier opening is usually only transient and quickly restored upon refeeding. Due to a rapid, dose-dependent, and prolonged decrease in absorption capacity for SCFA, however, any feed restriction increases the odds for postrestriction subacute ruminal acidosis. Inflammation due to acidosis can be alleviated by supplemental thiamine, yeasts, and plant bioactive (phytogenic) compounds. Butyrate is used in weaning calves to support ruminal barrier development; however, excess butyrate may promote hyperkeratosis, parakeratosis, and epithelial injury in the fully developed rumen of adult cows. Further research is needed to enhance the understanding of the various factors that counteract barrier impairment and help barrier restoration during acidogenic feeding, especially when concurring with unavoidable periods of feed restriction.     

Performance of neural networks for predicting yarn properties using principal component analysis

In recent years, neural networks have been used as a tool for modeling an industrial process. An improvement in their performance may be expected either by divining more efficient training algorithms or by intelligently manipulating the data set. The second method is examined. The problem chosen is one of predicting the properties of cotton yarn from the fiber properties. When the input data are known to correlate with each other, principal component analysis can be used to improve the performance of neural networks. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 91: 1746–1751, 2004     

Optimal Dynamic Monitoring Network Design and Identification of Unknown Groundwater Pollution Sources

The identification of unknown pollution sources is a prerequisite for designing of a remediation strategy. In most of the real world situations, it is difficult to identify the pollution sources without a scientifically designed efficient monitoring network. The locations of the contaminant concentration measurement sites would determine the efficiency of the unknown source identification process to a large extent. Therefore coupled and iterative sequential source identification and dynamic monitoring network design framework is developed. The coupled approach provides a framework for necessary sequential exchange of information between monitoring network and source identification methodology. The preliminary identification of unknown sources, based on limited concentration data from existing arbitrarily located wells provides the initial rough estimate of the source fluxes. These identified source fluxes are then utilized for designing an optimal monitoring network for the first stage. Both the monitoring network and source identification process is repeated by sequential identification of sources and design of monitoring network which provides the feedback information. In the optimal source identification model, the Jacobian matrix which is the determinant for the search direction in the nonlinear optimization model links the groundwater flow-transport simulator and the optimization method. For the optimal monitoring network design, the integer programming based optimal design model requires as input, simulated sets of concentration data. In the proposed methodology, the concentration measurement data from the designed and implemented monitoring network are used as feedback information for sequential identification of unknown pollution sources. The potential applicability of the developed methodology is demonstrated for an illustrative study area.     

Catalytic properties of dendron–OMS hybrids

The synthesis and catalytic testing of several dendron–ordered mesoporous silica hybrids are reported. These materials are active in both the nitroaldol (Henry) reaction and the transesterification of glyceryl tributyrate to afford methyl esters. In both reactions it is observed that dendrons terminated with primary amines are more catalytically active than samples containing dendrons terminated with secondary amines. On a mmol nitrogen per gram of silica basis, the first generation dendrons are the most active for both chemistries, and the SBA-15 samples display a higher activity than the MCM-41 samples. The pore-size effect observed is consistent with significant diffusion resistance in the MCM-41 samples. The activity trend observed in the SBA-15 materials is consistent with decreased cooperative effects between the amines and surface silanols as the dendrons become larger. Clear trends are observed indicating that higher generation dendrons are more selective to alcohol formation in the Henry reaction. The dendron catalysts are much more active and stable than simple amines attached to silica in the transesterification of triglycerides. Preliminary results shown indicate that these materials can also catalyze more demanding chemistries, an example of which is the Aldol condensation of 5-(hydroxymethyl)furfural and acetone. The results shown indicate that dendron–OMS hybrids can serve as effective solid base catalysts for a diverse range of chemistries.     

Performance analysis of a solar photovoltaic operated domestic refrigerator

This paper describes the fabrication, experimentation and simulation stages of converting a 165 l domestic electric refrigerator to a solar powered one. A conventional domestic refrigerator was chosen for this purpose and was redesigned by adding battery bank, inverter and transformer, and powered by solar photovoltaic (SPV) panels. Various performance tests were carried out to study the performance of the system. The coefficient of performance (COP) was observed to decrease with time from morning to afternoon and a maximum COP of 2.102 was observed at 7 AM. Simulations regarding economic feasibility of the system for the climatic conditions of Jaipur city (India) were also carried out using RETScreen 4. It was observed that the system can only be economically viable with carbon trading option taken into account, and an initial subsidy or a reduction in the component costs – mainly SPV panels and battery bank.     

Synthesis and Biological Evaluation of Chromium Bioorganometallics Based on the Antibiotic Platensimycin Lead Structure

The recent discovery of the natural product platensimycin as a new antibiotic lead structure has triggered the synthesis of numerous organic derivatives for structure–activity relationship studies. Herein, we describe the synthesis, characterization and biological evaluation of the first organometallic antibiotic inspired by platensimycin. Two bioorganometallic compounds containing (η⁶‐pentamethylbenzene)Cr(CO)₃ ( 2 ) and (η⁶‐benzene)Cr(CO)₃ ( 3 ), linked by an amide bond to the aromatic part of platensimycin, were synthesized. Their antibiotic activities were tested against B. subtilis 168 (Gram positive) and E. coli W3110 (Gram negative) bacterial strains. Both compounds were found to be inactive against E. coli but derivative 2 inhibits B. subtilis growth at a moderate MIC value of 0.15 mM . To test the intrinsic toxicity of chromium, several chromium salts along with {η⁶‐(3‐pentamethylphenyl propionic acid)}Cr(CO)₃ ( 5 ) and {η⁶‐(3‐phenyl propionic acid)}Cr(CO)₃ ( 6 ) were tested against both bacterial strains. No activity was observed against E. coli for any of the compounds; B. subtilis growth was not inhibited by Cr(NO₃)₃ and only very weakly by 5 , K₂Cr₂O₇ and Na₂CrO₄ at MIC values of 0.5, 0.68 and 1.24 mM , respectively. Compounds 2 , 3 , 5 and 4 (the pure organic analogue of 2 ) show similar cytotoxicity against HeLa, HepG2 and HT‐29 mammalian cell lines. Furthermore, the cellular uptake and the intracellular distribution of compounds 2 , 3 and Cr(NO₃)₃ in B. subtilis were studied using atomic absorption spectroscopy to gain insight in to the possible cellular targets. Compound 2 was found to be readily taken up and distributed almost equally among cytosol, cell debris and cell membrane in B. subtilis.     

Development of Breathing Rat-Lung Models for Particulate Deposition Studies

ABSTRACT

Techniques have been developed for casting both solid and hollow lung models from rat-lung specimens. To make a solid model, an air line at a positive pressure of 25 cm of water was connected to the trachea to air-dry lungs which had been removed surgically from the animal. Using the lost wax technique, a hollow cast of the airways and the nasopharynx was made. A mechanical breathing system, capable of simulating different breathing patterns, was developed.     

The case for technology in developing regions

Alongside good governance, technology is considered among the greatest enablers for improved quality of life. However, the majority of its benefits have been concentrated in industrialized nations and therefore limited to a fraction of the world's population. We believe that technology has a large role to play in developing regions, that "First World" technology to date has been a poor fit in these areas, and that there is thus a need for technology research for developing regions. Despite the relative infancy of technology studies in developing regions, anecdotal evidence suggests that access to technology has a beneficial economic impact. Cellular telephony is probably the most visible application, but there are many others, some of which we cover in this article. The World Bank's infoDev site catalogs hundreds of information and communications technologies (ICT) projects, albeit not all successful. Most of these projects use existing off-the-shelf technology designed for the industrialized world. Although it is clear that there are large differences in assumptions related to cost, power, and usage, there has been little work on how technology needs in developing regions differ from those of industrialized nations. We argue that Western market forces continue to meet the needs of developing regions accidentally at best.